Brief Intervention for Substance Using Native Youth is a 5-year research project designed to develop and test a school-based, brief motivational intervention for substance using, Native American high school students. Motivational Interviewing (MI) is a behavioral treatment for substance use problems that has already shown efficacy in some populations. Clinical trials support the effectiveness of MI with adults and older adolescents with substance use problems. However, MI clinical trials to date have been limited by (a) insufficient ethnic/racial diversity of samples (i.e., almost every MI RCT published to date has focused on predominantly non-Hispanic white samples), (b) lack of attention to non-treatment seeking populations, (c) no direct examination of putative mechanisms of change, and (d) no direct examination of how culture-related variables may influence treatment response. MI's effectiveness for minority populations, and especially Native American populations, has received scant research attention, and remains unknown. Moreover, Native American youth, compared to youth from other racial/ethnic backgrounds, are at especially high risk for drug use and drinking, which makes them particularly susceptible to the development of substance use problems. The primary goal of the proposed study is to conduct a clinical trial evaluating a culturally congruent, school-based motivational interviewing intervention targeting substance use among Native American high school students. The development phase of the project (6 months) will focus on (a) adapting our assessment and intervention materials in order to ensure cultural and developmental congruency with our target population, (b) training staff in conducting MI assessment and intervention with developmental and cultural sensitivity, and (c) collaborating with school and tribal representatives in the planning and implementation the clinical trial phase of the project. Clinical trial participants will be recruited from three predominantly Native American public high schools located in Oklahoma. A school-wide paper-and-pencil substance use screening questionnaire will be used to select a sample of high risk substance users (n = 480), who will be randomly assigned to one of three treatment conditions: (1) brief advice and a personalized feedback report alone (BA+PFR; n = 160), (2) brief advice, a personalized feedback report, and motivational interviewing (BA+PFR+MI; n =160), or (3) brief advice, a personalized feedback report, motivational interviewing, and a 6-months post- intervention booster session (BA+PFR+MI+BOOST; n =160). Participants will be evaluated at study entry, and at 3-, 6-, 9-, and 12-month follow-ups. We hypothesize Native American high school students who receive motivational interviewing will demonstrate significantly greater post-intervention reductions in substance use and substance- related negative consequences than their counterparts who do not receive MI (i.e., BA+PFR participants). We also hypothesize adolescents who receive the booster session will demonstrate significantly greater and longer-lived substance use reductions than adolescents who do not receive the booster. A secondary aim is to examine mechanisms of change (i.e., mediators) associated with MI response. We hypothesize pre-to post-intervention changes in perceived readiness to change, perceived importance of change, and self-efficacy will predict participants' response to intervention. Our third aim is to explore gender and Native American-specific cultural variables (Cherokee self- reliance & Native American ethnic identity) as moderators of the differential effectiveness of MI; this aim is specifically designed as a preliminary evaluation of the gender and cultural invariance of our school-based MI intervention. We believe our proposed study is significant and innovative, and represents an important next step in the development of cross-culturally effective, brief, and school- based interventions for drug use and drinking among teenagers.